Changes in withdrawal-related emergency department use after medetomidine emerged in Philadelphia’s drug supply, 2022–2025: an interrupted time-series analysis

Abstract Background Drug-related morbidity and mortality remain high in Philadelphia, and clinical care of persons who use drugs is complicated by a constantly changing illicit drug supply. Medetomidine is a potent α-2 adrenergic agonist sedative used in veterinary medicine. It was introduced to Philadelphia’s illicit drug supply during spring 2024 and most often detected in fentanyl samples. By late 2024, the Philadelphia Department of Public Health received reports from emergency department (ED) clinicians of patients presenting with severe withdrawal hypothesized to be linked to medetomidine. These presentations differed from known opioid or xylazine withdrawal patterns and were not responsive to standard treatment protocols. We evaluated withdrawal-related ED visit trends before and after medetomidine's emergence to guide clinical and public health response. Methods Using syndromic surveillance data, we conducted an interrupted time-series analysis of weekly ED visit proportions for withdrawal patients during January 2022–December 2025. Visits were identified using International Classification of Diseases, Tenth Revision codes for opioid withdrawal (F11.13, F11.23, F11.93), used as a proxy absent medetomidine-specific codes. We applied autoregressive integrated moving average models to estimate weekly changes in withdrawal-related ED visits/10,000 ED visits after medetomidine’s first detection, with April 28, 2024, defined as the index week. Models were adjusted for weekly mean patient age and proportion of visits made by Philadelphia residents. Results 10,019 withdrawal-related ED visits were reported, averaging 48 visits/week. Immediately after medetomidine’s detection, no statistically significant change in withdrawal-related ED visits proportions was observed. However, during the subsequent 87 weeks, proportions increased significantly by 0.74/10,000 ED visits/week (95% CI: 0.68–0.80), corresponding to a 6.3% weekly increase (95% CI: 5.8%–6.8%). Results were unchanged after demographic adjustment. Conclusion Consistent with patterns seen when new substances enter the illicit drug market, withdrawal-related ED visit proportions remained low around the time medetomidine emerged. Over time, a significant and sustained increase was observed, suggesting medetomidine might contribute to worsening withdrawal presentations as its presence in the drug supply grows. These findings highlight the need for continued drug supply surveillance, continued toxicologic testing to better establish causality, and adaptation of existing withdrawal treatment protocols to address clinical strategies posed by medetomidine.